Melanoma vaccine candidates from chimeric hepatitis B core virus-like particles carrying a tumor-associated MAGE-3 epitope.
Vaccination of melanoma patients with tumor-specific antigens recognized by cytotoxic T lymphocytes (CTLs) may produce significant tumor regressions. Here, we suggest a novel type of tumor vaccines, with well-studied CTL epitopes presented on highly immunogenic virus-like particle (VLP) carriers. Cancer-germline gene MAGE-3 encodes for an antigenic nonapeptide (MAGE-3(168-176) peptide) that is recognized by CTLs on human leukocyte antigen (HLA)-A1 and HLA-B35 molecules. A set of recombinant genes encoding hepatitis B virus core protein carrying MAGE-3 epitope was constructed and expressed in Escherichia coli cells. Variants that led to formation of chimeric VLPs in vivo were purified and analyzed for their DNA binding properties in vitro. VLPs exhibiting the most pronounced nucleic acid binding affinity were selected and loaded either with single-stranded DNA oligodeoxynucleotides rich in nonmethylated CG motifs, or with longer double-stranded DNA fragments. Packaged DNA was protected, at least partially, against the action of bacterial DNase. Such highly purified chimeric VLPs with entrapped immunomodulatory sequences could possibly be used as antitumor vaccines.
Kazaks
Andris
A
Latvian Biomedical Research and Study Center, Riga, Latvia. andris@biomed.lu.lv
Balmaks
Reinis
R
Voronkova
Tatyana
T
Ose
Velta
V
Pumpens
Paul
P
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D003001:Cloning, Molecular; D018899:CpG Islands; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000628:therapy*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006512:Hepatitis B Core Antigens; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic